Year: 2018
Type: dissertation
Abstract: Angiomotin (AMOT) is a scaffolding protein involved in cell polarity regulation, cell migration and early embryo lineage differentiation, yet its biological significance in the human placenta remains unknown. I hypothesized that AMOT controls trophoblast cell polarity and migration, and is further regulated by transforming growth factor beta (TGF) signalling and upstream oxygen tension. AMOT localization to extravillous trophoblast (EVT) cells, corroborated by AMOT 80 overexpression increasing JEG3 cell migration rate, supports a role for AMOT in EVT migration. TGF1/3 treatment decreased AMOT protein levels and redistributed AMOT from the tight-junction to cytoplasmic F-actin in JEG3 cells. TGF1/3 also prompted a novel association between AMOT 80 and Partitioning Defective Protein-6. Similarly, low oxygen exposure negatively regulated AMOT levels and localization. Furthermore, Jumonji C Domain Containing Protein-6 (JMJD6), an oxygen sensor, was discovered to positively regulate AMOT via lysyl hydroxylation. Finally, AMOT levels were found markedly reduced in preeclampsia, a disease characterized by aberrant TGF signalling and chronic hypoxia. In conclusion, this study reveals AMOT is a mediator of TGF and oxygen signalling to regulate trophoblast migration in the human placenta.
Source: TSpace (University of Toronto)
Author: Abby Farrell
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W3026506033